Noble, Caroline F.
Rebello Pinho, Joao R.
Malta, Fernanda M.
Gomes-Gouvea, Michele S.
Alvarado-Mora, Monica V.
da Silva, Mariliza H.
Leite, Andrea G. B.
Piccoli, Leonora Z.
Rodrigues, Flaviane K.
Carrilho, Flair J.
Mendes-Correa, Maria C.
Total Authors: 12
 Univ Sao Paulo, Sch Med, Dept Infect Dis, Sao Paulo, SP - Brazil
 Univ Sao Paulo, Sch Med, Lab Trop Gastroenterol & Hepatol Joao Alves de Qu, LIM 07, Inst Trop Med, Dept Gastroenterol, Sao Paulo, SP - Brazil
 Hosp Israelita Albert Einstein, Albert Einstein Med Diagnost, Sao Paulo, SP - Brazil
 Ctr Referencia & Treinamento DST AIDS Estado Sao, Sao Paulo, SP - Brazil
 Clin Especialidades, Sao Bernardo Do Campo, SP - Brazil
 Ctr Especializado Saude, Caxias Do Sul, RS - Brazil
 ABC Fdn Med Sch, Infect Dis Res Unit, Santo Andre, SP - Brazil
Total Affiliations: 7
Web of Science Citations:
Background: HCV has a high replication rate and a lack of proofreading activity, leading to a greatly diverse viral population. This diversity may lead to emergence of resistant strains in direct-acting antiviral therapy. The frequency of naturally occurring HCV protease inhibitor (PI) mutations has been addressed in many countries, but there are few data on the prevalence of these mutations in Brazilian patients. Methods: We evaluated the sequence of HCV NS3 protease gene in 247 patients (135 HCV-monoinfected and 112 HIV-HCV-coinfected patients). HCV RNA was extracted from plasma and a fragment of 765 base pairs from the NS3 region was amplified and sequenced with Sanger-based technology. Results: HIV-HCV-coinfected patients were more likely to be older than 40 years and have an HCV subtype-1a infection. Overall, 21.9% of patients had at least one amino acid substitution in the NS3 region; 14 patients (5.7%) harboured at least one resistance mutation (T54S, V55A, Q80R) and the Q80K mutation was not found in our case series. There was no difference between monoinfected and coinfected patients regarding the frequency of natural polymorphisms and resistance mutations. Conclusions: Baseline HCV NS3 amino acid substitutions identified herein are considered mostly natural polymorphisms with no clinical impact on PI-based therapy. The identified resistance mutations may be associated with low-level resistance to PIs in vitro. Q80K substitution seems to be a rare event in Brazil. HIV coinfection was not associated with a greater frequency of such substitutions in the studied sample. (AU)